ABSTRACT Scientific Premise. One million homeless youth smoke --70% of the population. Not only do homeless youth smoke at a rate 2.5 times higher than other youth populations, they engage in riskier smoking practices. Many homeless youth want to stop smoking, but most who attempt to quit do so without supported intervention. No known study has focused on smoking cessation effectiveness with homeless youth?a notable public health oversight. As the NCI Tobacco Control Research Priorities working group has noted, there have been few scientific advances in tobacco treatment in the past 20 years. Moreover, disparities in tobacco use between privileged and vulnerable populations have increased due to differential rates in access and treatment response to existent tobacco cessation intervention. Training Plan. Through this K07 career development grant, Dr. Nemeth will receive direct training in addiction and novel behavioral intervention science, and application of this knowledge to mentored research implementation, to optimize a contextually tailored cessation intervention for homeless youth. The mentoring team includes NIH-funded researchers with expertise in community-based intervention development for homeless youth and methodological approaches to the development of novel tobacco cessation strategies endorsed by the NCI. The overall training plan will equip Dr. Nemeth with skills to implement cessation intervention development studies with vulnerable youth populations using Multiphase Optimization STrategy (MOST) methodology. Mentored Research. Specific Aim 1 will establish a theoretical framework for cessation among homeless youth incorporating phase-specific capabilities and opportunities impacting motivation to engage in cessation (MOST Step 1). Using qualitative and quantitative approaches, Specific Aim 1 will determine: (1) What internal capabilities and social and physical environmental opportunities need to be in place for homeless youth smokers to be motivated to quit and engage supported treatment (Aim 1a); (2) What conditions internal to homeless youth smokers, and in their social and physical environment, are associated with 1) motivation to quit and 2) past quit attempts? (Aim 1b). Guided by the theoretical framework for cessation among homeless youth, Specific Aim 2 will identify a set of cessation intervention components and assess their implementation feasibility (MOST Step 2). This aim will apply a theoretical framework for smoking cessation among homeless youth in order to: (1) identify a set of cessation intervention components to test for effect on abstinence in future study (Aim 2a); and (2) assess acceptability and feasibility of cessation component implementation among homeless youth smokers and among their service providers (Aim 2b). This work has strong potential to reduce subsequent morbidity and mortality caused by smoking among homeless youth. Transition to Research Independence. This applied approach responds to a key scientific goal recommended by the NCI Tobacco Control Research Priorities working group that aims to increase access to, and the effectiveness of, behavioral health tobacco cessation treatment for high-risk populations. The training and mentored research plan will establish Dr. Nemeth as a tobacco control intervention scientist positioned to implement NIH-funded research in the optimization of multi-component behavioral interventions with highly traumatized and vulnerable youth populations.